In vivo modulation of platelet deposition on human atherosclerotic lesions by various antiaggregatory prostaglandins

The influence of intravenous infusions of various prostaglandins on in vivo platelet function was studied after labelling of autologous platelets with 100 mu ci 111 indium-oxinesulfate in patients with peripheral vascular disease stage II according to FONTAINE. PGI2 (5 ng/kg/min) provoked a significant decrease of platelet deposition and a prolongation in platelet half-life time (74 +/- 6 vs 68 +/- 5 hours). PGE1 (25 ng/kg/min) failed to influence platelet deposition, but prolonged significantly platelet half-life time (82 +/- 6 vs 76 +/- 8 hours). CG 4203 (25 ng/kg/min) decreased significantly platelet deposition and prolonged significantly platelet half-life time (73 +/- 10 vs 67 +/- 11 hours). Iloprost (1 and 2 ng/kg/min) reduced significantly platelet deposition without dose relation. Half-life time was increased significantly after therapy compared to placebo (1 ng: 76 +/- 7 vs 69 +/- 7; 2 ng: 73 +/- 9 vs 67 +/- 9 hours).     

Do human platelets express COX-2?

The rate-limiting enzyme in prostaglandin (PG)- and thromboxane (TX)-synthesis is known as cyclooxygenase (COX). The COX-enzyme family consists of the classical COX-1 and the inducible COX-2-enzyme. To investigate whether platelets contain COX-2, we measured thiobarbituric acid reactive substances (TBARS) after either blocking COX-1 or COX-2 or adding compounds known to affect COX-expression. To stimulate platelets' different reagents such as collagen, thrombin and arachidonic acid (AA) were used. The inhibitors used in this study were acetylsalicylic acid (ASA), indomethacin and NS-398. Using the western-blot technique, we failed to detect COX-2 in platelets while COX-1 was detectable. We were not able to discover COX-2 in platelets using the methods we applied. As the amount of COX-2 in platelets might be below the detection limit of the methods used, the biological relevance COX-2 in platelets, if even existing at low amounts, remains to be established.